PVSRIPO in Recurrent Malignant Glioma

• ClinicalTrials.gov Identifier: NCT02986178
• Recruitment Status: Active, not recruiting
• First Posted: December 8, 2016
• Last Update Posted: June 18, 2020
• Sponsor: Istari Oncology, Inc.
• Collaborator: Duke University
• Information provided by (Responsible Party): Istari Oncology, Inc.

Study Description

Brief Summary:

This is a phase 2 study of oncolytic polio/rhinovirus recombinant (PVSRIPO) in adult patients with recurrent World Health Organization (WHO) grade IV malignant glioma.

Condition or disease	Intervention/treatment	Phase
Malignant Glioma	Biological: PVSRIPO	Phase 2

Detailed Description:

This is a Phase 2 study of oncolytic polio/rhinovirus recombinant (PVSRIPO) in adult patients with recurrent World Health Organization (WHO) grade IV malignant glioma. The objective of this study is to investigate the safety and efficacy (anti-tumor response and survival) of PVSRIPO in recurrent WHO grade IV malignant glioma.

Patients will be administered PVSRIPO intratumorally via convection-enhanced delivery (CED) using an intracerebral catheter placed within the enhancing portion of the tumor. Retreatment with PVSRIPO is allowed, provided retreatment eligibility criteria are met.

All patients who receive PVSRIPO treatment will be included in efficacy and safety analyses.

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 122 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Multicenter Phase 2 Study of Oncolytic Polio/Rhinovirus Recombinant (PVSRIPO) in Recurrent WHO Grade IV Malignant Glioma Patients
• Actual Study Start Date: June 1, 2017
• Estimated Primary Completion Date: August 2023
• Estimated Study Completion Date: December 2023

Arms and Interventions

Arm	Intervention/treatment
Experimental: Polio/Rhinovirus Recombinant (PVSRIPO); Polio/Rhinovirus Recombinant (PVSRIPO)	Biological: PVSRIPO; A single dose of an oncolytic polio/rhinovirus recombinant (PVSRIPO)

Outcome Measures

Primary Outcome Measures :

1. Objective Radiographic Response Rate [ Time Frame: 24 months after initial PVSRIPO infusion and through study completion. ]
   Assess objective anti-tumor response based on iRANO criteria.
2. Objective Radiographic Response Rate [ Time Frame: 36 months after initial PVSRIPO infusion and through study completion. ]
   Assess objective anti-tumor response based on iRANO criteria.
3. Duration of Objective Radiographic Response [ Time Frame: 24 months after initial PVSRIPO infusion and through study completion. ]
   Assess time of confirmed response to confirmed progressive disease/death.
4. Duration of Objective Radiographic Response [ Time Frame: 36 months after initial PVSRIPO infusion and through study completion. ]
   Assess time of confirmed response to confirmed progressive disease/death.

Secondary Outcome Measures :

1. Overall Survival [ Time Frame: 24 and 36 months after initial PVSRIPO infusion and through study completion. ]
   Overall Survival, relative to external control group(s)
2. Landmark Survival [ Time Frame: 24 and 36 months post-infusion and through study completion. ]
   Overall survival at 24 and 36 months and greater
3. Disease Control Rate Following PVSRIPO Infusion [ Time Frame: 24 and 36 months after initial PVSRIPO infusion and through study completion. ]
   The percentage of patients classified as non-progressive by radiographic response based on standard criteria.
4. Safety of PVSRIPO: proportion of patients who experience grade 3, 4, or 5 AEs [ Time Frame: While on study; average of 12 to 36 months after initial PVSRIPO infusion. ]
   Within each cohort for those randomized prior to protocol version 7, as well as for those patients retreated with PVSRIPO, the proportion of patients who experience grade 3, 4, or 5 AEs that are possibly, probably, and definitely related to protocol treatment will be estimated.

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

INCLUSION CRITERIA SUMMARY:

1. Patients must have a recurrent (first or second recurrence only, including this recurrence; transformation from a lower grade tumor to a WHO grade IV malignant glioma will be considered a first recurrence) supratentorial WHO grade IV malignant glioma based on imaging studies with measurable disease (a minimum measurement of 1 cm and maximum of 5.5 cm of contrast-enhancing tumor) with prior histopathology consistent with a WHO grade IV malignant glioma confirmed by the site's neuropathologist or the neuropathologist's designate.
2. Male patients who are sexually active are eligible if he and/or his partner(s) meets the criteria outlined in the protocol. Female subjects are eligible if he and/or his partner(s) meets the criteria outlined in the protocol.
3. Age ≥ 18 years of age.
4. Karnofsky Performance Status (KPS) Score ≥ 70%.
5. Prothrombin and Partial Thromboplastin Times ≤ 1.2 x normal prior to biopsy.
6. Total bilirubin, serum glutamic oxaloacetic transaminase (SGOT), serum glutamic pyruvic transaminase (SGPT), alkaline phosphatase ≤ 2.5 x normal prior to biopsy.
7. Neutrophil count ≥ 1000 prior to biopsy.
8. Hemoglobin ≥ 9 prior to biopsy.
9. Platelet count ≥ 100,000/μL unsupported is necessary for eligibility on study; however, because of risks of intracranial hemorrhage with catheter placement, platelet count ≥ 125,000/μL is required for the patient to undergo biopsy and catheter insertion, which can be attained with the help of platelet transfusion.
10. Creatinine ≤ 1.2 x normal range prior to biopsy.
11. Positive serum anti-PV titer prior to biopsy.
12. The patient must have received a boost immunization with trivalent inactivated IPOL™ (Sanofi-Pasteur) at least 1 week, but less than 6 weeks, prior to administration of the study agent.
13. At the time of biopsy, prior to administration of virus, the presence of recurrent tumor must be confirmed by histopathological analysis.
14. A signed IRB-approve informed consent form (ICF).
15. Able to undergo brain MRI with and without contrast.

EXCLUSION CRITERIA SUMMARY:

1. Females who are pregnant or breast-feeding.
2. Patients with an impending, life-threatening cerebral herniation syndrome, based on the assessment of the study neurosurgeons, their designate, and the reviewer designated by the sponsor.
3. Patients with severe, active co-morbidity, defined as in the protocol.
4. Patients with a previous history of neurological complications due to PV infection.
5. Patients who have not recovered from the toxic effects of prior chemo- and/or radiation therapy. Guidelines for this recovery period are dependent upon the specific therapeutic agent being used.
6. Patients may not have received tumor treating fields (≤ 1 week), chemotherapy or bevacizumab ≤ 4 weeks [except for nitrosourea and lomustine (≤ 6 weeks); metronomic dosed chemotherapy, such as daily temozolomide, etoposide or cyclophosphamide (≤ 1 week)] prior to starting the study drug.
7. Patients may not have received immunotherapy ≤ 4 weeks prior to starting the study drug unless patients have recovered from side effects of such therapy.
8. Patients may not be less than 12 weeks from radiation therapy of the brain, unless progressive disease outside of the radiation field or 2 progressive scans at least 4 weeks apart or histopathologic confirmation.
9. Prior to enrollment, has not completed all standard of care treatments, including surgical procedure and radiation therapy (at least 59Gy) as outlined in the protocol.
10. Patients with neoplastic lesions in the brainstem, cerebellum, or spinal cord; radiological evidence of multiple areas of active (growing) disease (active multifocal disease); tumors with contrast-enhancing tumor component crossing the midline (crossing the corpus callosum); extensive subependymal disease (tumor touching subependymal space is allowed); or extensive leptomeningeal disease (tumor touching leptomeninges is allowed).
11. Patients with undetectable anti-tetanus toxoid immunoglobulin G (IgG).
12. Patients with known history of agammaglobulinemia.
13. Patients on greater than 4 mg per day of dexamethasone within the 2 weeks prior to admission for PVSRIPO infusion.
14. Patients with worsening steroid myopathy (history of gradual progression of bilateral proximal muscle weakness, and atrophy of proximal muscle groups).
15. Patients with prior, unrelated malignancy requiring current active treatment with the exception of cervical carcinoma in situ and adequately treated basal cell or squamous cell carcinoma of the skin.
16. For patients randomized prior to V7, a known history of hypersensitivity to lomustine, dacarbazine, or any components of lomustine.
17. Patients with active autoimmune disease requiring systemic immunomodulatory treatment within the past 3 months.

Contacts and Locations

Locations

United States, California

UCSF Neurological Surgery

San Francisco, California, United States, 94941

United States, Florida

Baptist MD Anderson Cancer Center

Jacksonville, Florida, United States, 32207

United States, Massachusetts

Massachusetts General Hospital

Boston, Massachusetts, United States, 02114

Dana-Farber Cancer Institute

Boston, Massachusetts, United States, 02215

United States, North Carolina

Preston Robert Tisch Brain Tumor Center at Duke University

Durham, North Carolina, United States, 27710

United States, Ohio

University Hospitals Cleveland Medical Center

Cleveland, Ohio, United States, 44106

Sponsors and Collaborators

Istari Oncology, Inc.

Duke University

Investigators

• Principal Investigator: Dina Randazzo, DO; Duke University

More Information

Additional Information:

The Preston Robert Tisch Brain Tumor Center at Duke University 

• Responsible Party: Istari Oncology, Inc.
• ClinicalTrials.gov Identifier: NCT02986178
• Other Study ID Numbers: Pro00077024
• First Posted: December 8, 2016
• Last Update Posted: June 18, 2020
• Last Verified: June 2020

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Istari Oncology, Inc.:

Glioblastoma; Glioma; PVSRIPO; Duke; Pro00077024; Brain tumor; Istari; Recurrent; GBM; rGBM

Additional relevant MeSH terms:

Glioma; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Glandular and Epithelial; Neoplasms, Nerve Tissue